Data from the American Cancer Society suggests that prostate cancer (PC) is the leading non-cutaneous cancer diagnosis in males in 2018 in the US with 164,690 estimated new cases and has the third highest mortality with 29,430 estimated deaths. Current testing methods for detection of PC and for assessment of response to local targeted therapy such as PSA measurements do not have the necessary precision that is essential for further disease management. After therapy, assessment of success by PSA testing, MRI and biopsy are unreliable because PSA levels are confounded by residual prostate tissue, MRI is confounded by treatment effects, and repeat systematic biopsies are invasive and may not thoroughly sample all relevant tissue. There is a significant need for better tools to assess immediate response and detect early recurrence. This project will take a targeted approach to improving the detection of PC, with a focus on early detection of sites of disease that can be treated with local targeted therapy, as well as on assessment of response to these therapies and prediction of progression-free survival at 24 months. 68Ga-RM2 is a synthetic bombesin receptor antagonist, which targets gastrin-releasing peptide receptors (GRPr). GRPr are highly overexpressed in several human tumors, including PC. Because of their low expression in BPH and inflammatory prostatic tissues, imaging of GRPr has potential advantages over current choline- and acetate-based radiotracers. In our experience, 68Ga-RM2 identified all primary lesions in 15 men with PC scheduled for radical prostatectomy and had a 70% detection rate in 80 men with biochemical recurrence (mean PSA: 8.0 ng/dl) and negative conventional imaging (bone scan and CT or MRI). Prostate-specific membrane antigen (PSMA) is a cell surface protein significantly overexpressed in prostate cancer cells when compared to other PSMA-expressing tissues such as kidney, proximal small intestine or salivary glands. PSMA provides an excellent target for PC-specific imaging. Methods have been developed to label PSMA ligands with 68Ga, enabling their use for PET imaging. 68Ga-PSMA-11 PET can detect PC at both initial diagnosis and biochemical recurrence with high contrast by binding to the extracellular domain of PSMA. Better localization of cancer within the prostate itself may also have a clinical impact by guiding image-targeted biopsy and patient selection for local targeted therapy. While both 68Ga-RM2 and 68Ga-PSMA-11 can detect PC, their biodistribution is distinct due to their targeting of different biological processes involved in PC that do not overlap. Therefore, we will evaluate both 68Ga-RM2 PET/MRI and 68Ga-PSMA-11 PET/MRI for detection of PC and evaluation of response to local targeted therapy, as well as for prediction of progression-free survival at 24 months.